Changes in urinary excretions of cadmium, copper, and zinc in Japanese workers

The authors undertook this study to determine changes in the daily concentration of cadmium, copper, and zinc in Japanese workers' urine over a 13-year period from 1985 to 1998. The workers were aged between 20 and 59 years. The authors studied 277 subjects in 1985, 320 in 1993, and 292 in 1998, for a total of 889 (464 men and 425 women). Although. in both men and women, urinary excretions of cadmium and copper were lower in 1993 and 1998 than in 1985, they were not substantially lower in 1998 than in 1993. The authors observed no marked changes between 1985, 1993, and 1998 regarding the excretion of zinc in any of the age groups in either men or women. Furthermore, the excretion of urinary cadmium in 1998 still exceeded the tolerable limit levels in the general population of the investigated region in Japan. This fact suggests the necessity of further nationwide investigation and comprehensive measures to reduce cadmium exposure in Japanese society.     

Effects of aldehyde dehydrogenase-2 genotype on cardiovascular and endocrine responses to alcohol in young Japanese subjects

The present study was designed to investigate the effects of aldehyde dehydrogenase-2 (ALDH2) genotype on cardiovascular and endocrine responses to alcohol ingestion in young, healthy Japanese subjects. For this purpose, we monitored changes in the electrocardiogram (ECG), blood pressure (BP), finger blood flow (BF) and facial skin temperature (FST) during and after alcohol ingestion (0.4 ml/kg body weight). Spectral analyses of beat-to-beat variations of heart rate (HR), BP and BF were applied. Two major spectral components were examined at low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-10.4 Hz) bands for HR and BP variability (BPV). Significant effects for ALDH2 genotype were observed in HR variability (HRV) analysis; HF power of HRV was markedly depressed and the LF/HF ratio was significantly higher with alcohol in ALDH2-deficient (ND) subjects, while ALDH2-normal (NN) subjects did not display such changes. Analysis of BP variability showed increased LF and HF power after alcohol ingestion in the NN subjects, but there were no significant differences between genotypic groups. We also examined BF variability (BFV) in six major spectral components; power of the 0.8-2.2 Hz frequency band was significantly affected by genotype and higher power was observed in the ND subjects. Plasma concentrations of both epinephrine and norepinephrine increased after alcohol ingestion only in the ND subjects. Furthermore, plasma concentrations and urinary excretion of epinephrine, but not norepinephrine, were higher after alcohol ingestion in the ND than in the NN subjects. Blood acetaldehyde levels were about 10-fold higher in the ND than in the NN subjects although blood alcohol levels similarly increased in the ND and NN subjects. Our results also indicated that alcohol ingestion increased secretion of pituitary-adrenal hormones including ACTH, beta-endorphin and cortisol in the ND subjects. The present results along with previous studies suggest that alcohol-induced tachycardia in the ND subjects was probably mediated by acetaldehyde-induced rise in epinephrine secretion from the adrenal medulla and/or changes in the autonomic nervous system. Alcohol-induced relative predominance of cardiac sympathetic activity in the ND subjects might be ascribed partly to increased norepinephrine secretion from sympathetic nerve terminals. Effects of acetaldehyde on these cardiovascular and endocrine systems were discussed in terms of their effects on the central nervous system.     

Activity and distribution of learning-related neurons in monkey (Macaca fuscata) prefrontal cortex

The involvement of monkey (Macaca fuscata) prefrontal cortex (PFC) neurons in motor output decisions was studied by recording single neuron activity during 3 tasks: (a) go-left, go-right, or no-go decisions, (b) operant bar press feeding based on discrimination of food and nonfood, and (c) either delayed matching-to-sample (DMS) or DMS with response delay. Combinations of single neuron responses during the 3 tasks suggested 7 types of PFC neurons that were related to attention, choice, task-unique memory, reward anticipation, laterality, initiation of movement, and suppression of movement. The authors suggest that responses of PFC neurons do not depend on physical properties of the stimuli, but on their behavioral significance. PFC neurons might be important for appropriate behavior in response to external stimuli and internal or motivational factors.     

Significance of elevated urinary human intestinal alkaline phosphatase in Japanese people exposed to environmental cadmium

Urinary human intestinal alkaline phosphatase (IAP),β₂-microglobulin (β₂-MG) and N-acetyl-β-d-glucosaminidase (NAG) were analyzed in 40 Japanese environmental-cadmium (Cd)-exposed and 40 non-exposed subjects to evaluate early biological markers for Cd-induced renal damage. All urinary indicators were significantly higher in the Cdexposed subjects than non-exposed subjects. A fourth-order function was fitted for the relationship between β₂-MG and IAP or NAG. The β₂-MG concentration corresponding to the inflexion point for IAP was smaller than that for NAG. This result may support the contention that the cells containing IAP are damaged earlier than those containing NAG, and that IAP is a useful marker for detecting renal tubular dysfunction in people moderately exposed to Cd. However, in the stage of severe renal damage, the combination of IAP and β₂-MG is considered to be more useful.     

Interaction of caffeine with L-tryptophan: study by 1H nuclear magnetic resonance spectroscopy

The interaction of caffeine with L-tryptophan was investigated in aqueous solution adjusted to an ionic strength of 0.20, at pH 6.2, by using 1H NMR spectroscopy. Caffeine interacted with L-tryptophan at a molar ratio of 1:1 by parallel stacking. The thermodynamic parameters obtained for the complexation were as follows: delta G degree = -1.70 kcal/mol at 25 degrees C (K = 17.6 M-1), delta H degree = -3.7 kcal/mol, delta S degree = -6.7 eu. It was found that the driving force for parallel stacking is a combination of electrostatic, polarization, and dispersion interactions, and the contribution of hydrophobic bonding is not large. A possible stacking mode is postulated based on the complexation shifts and pi-electron charge distributions of caffeine and L-tryptophan.     

Effects of nonsaponin fraction of red ginseng on learning deficits in aged rats

Previously we reported that oral application of red ginseng significantly ameliorated learning deficits in aged rats and young rats with hippocampal lesions. In the present study, we investigated the effects of the nonsaponin fraction of red ginseng on learning deficits in aged rats in behavioral studies and those on long-term potentiation (LTP) in the hippocampal CA3 subfield in young rats in electrophysiological studies. In the behavioral studies, three groups of rats [aged rats with and without oral administration of the nonsaponin fraction of red ginseng and young rats] were tested with the three types of spatial-learning task [distance movement task (DMT), random-reward place search task (RRPST), and place-learning task (PLT)] in a circular open field. The results in the DMT and RRPST indicated that motivational and motor activity was not significantly different among the three groups of rats. However, performance of the aged rats without nonsaponin was significantly impaired in the PLT when compared with the young rats. Treatment with nonsaponin significantly ameliorated deficits in place-navigation learning in the aged rats in the PLT. In the electrophysiological studies, effects of nonsaponin on the LTP in the CA3 subfield of the hippocampal slices were investigated in vitro. Pretreatment with nonsaponin significantly augmented the increase in population spike amplitudes in the CA3 subfield after LTP induction. These results suggest that the nonsaponin fraction of red ginseng contains important substances to improve learning and memory in aged rats and that this amelioration by nonsaponin might be attributed partly to augmentation of LTP in the CA3 subfield.     

Benchmark dose of cadmium concentration in rice for renal effects in a cadmium‐polluted area in Japan

The aim of this study was to estimate the reference level of cadmium in rice as the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) for various renal effects by applying an updated hybrid approach. The participants were 1120 men and 1274 women aged 50 years or older who lived in the environmentally exposed Kakehashi river basin for at least 30 years. As indicators of renal dysfunction, glucose, protein, aminonitrogen, metallothionein and β₂‐microgrobulin in urine were measured. Cadmium concentration was determined for rice samples stored in warehouses of the farmers in all of the polluted hamlets. The BMD and BMDL that corresponded to an additional risk of 5% were calculated with background risk at a zero exposure set at 5%. The obtained BMDLs were 0.39 (aminonitrogen), 0.26 (metallothionein), 0.25 (β₂‐microgrobulin) mg kg^–1 in men and 0.44 (glucose), 0.32 (protein), 0.33 (aminonitrogen), 0.28 (metallothionein) and 0.24 (β₂‐microgrobulin) mg kg^–1 in women. The lowest BMDL was 0.25 and 0.24 mg kg^–1 (β₂‐microgrobulin) in men and women respectively. These values were lower than the maximum level (0.4 mg kg^–1) determined by the Codex Alimentarius Commission, indicating that these BMDLs may contribute to further discussion on the health risk assessment of cadmium exposure. Copyright © 2014 John Wiley & Sons, Ltd.     

Place‐related neuronal activity in the monkey parahippocampal gyrus and hippocampal formation during virtual navigation

Neuropsychological data in primates demonstrated a pivotal role of the hippocampal formation (HF) and parahippocampal gyrus (PH) in navigation and episodic memory. To investigate the role of HF and PH neurons in environmental scaling in primates, we recorded neuronal activities in the monkey HF and PH during virtual navigation (VN) and pointer translocation (PT) tasks. The monkeys had to navigate within three differently sized virtual spaces with the same spatial cues (VN task) or move a pointer on a screen (PT task) by manipulating a joystick to receive a reward. Of the 234 recorded neurons, 170 and 61 neurons displayed place‐related activities in the VN and PT tasks, respectively. Significant differences were observed between the HF and PH neurons. The spatial similarity of place fields between the two different virtual spaces was lower in PH than in HF, while specificities of the neuronal responses to distal spatial cues were higher in PH than in HF. Spatial view information was predominately processed in posterior PH. The spatial scales (place field sizes) of the HF and PH neurons were reduced in the reduced virtual space, as shown in rodent place cells. These results suggest the complementary roles of HF (allocentric representation of landmarks) and PH (representation of the spatial layout of landmarks) in the recognition of a location during navigation. © 2013 Wiley Periodicals, Inc.     

大鼠杏仁体基底外侧核中含D2受体的γ-氨基丁酸神经元受多巴胺能末梢支配

杏仁体中的多巴胺(DA)和γ -氨基丁酸(GABA)递质系统均参与精神分裂症的病理过程,临床上一般用多巴胺II型受体(D2)阻断剂予以治疗。然而,目前尚不清楚GABA与D2受体是否共存,也不清楚DA能神经末梢与GABA能神经元之间的联系方式。本实验用共聚焦激光扫描显微镜(CLSM)和免疫电镜(IEM)研究了杏仁体关键性核团基底外侧核中GABA与D2受体的共存关系以及DA神经能末梢与GABA能神经元之间的突触关系。CLSM显示由谷氨酸脱羧酶(GAD)标记的GABA能神经元全部对D2受体呈免疫阳性反应,表明GABA能神经元含有D2受体。IEM显示,在 980个DA能神经末梢形成的突触中,45%的突触是由DA免疫反应阳性神经末梢直接(36% )或间接(9% )与GAD免疫反应阳性神经元的树突形成,另 55%是由DA免疫反应阳性神经末梢与未标记的神经元成分形成。DA GABA的直接性突触进而可区分为单突触 (16% )、汇聚突触 (14% )及轴 轴突触(6% )。而DA- GABA的间接性突触是个突触复合体。在该复合体中,DA免疫反应阳性末梢在一个未标记的末梢上形成对称性突触,而该未标记末梢又与GAD免疫反应阳性树突形成非对称性突触。在DA与未标记神经元成分之间的突触中,AD免疫反应阳性末梢分别与未标记胞体(4% )、树突(42% )及轴突末梢(9% )形成突触。所有DA突触无一例外均为?